OVERALL DESCRIPTION (provided by applicant): This program continues to study molecular differences between tumors and normal tissues and how they change during treatment. Advances in the molecular biology of cancer are leading to new treatment options but have not yielded an anticipated improvement in prognosis for patients with solid tumors. One problem has been the limited ability to objectively evaluate the effectiveness of new therapies in clinical trials. We respond to this challenge by using molecular imaging to evaluate response to treatments. There are two promising roles for imaging: 1) Early assessment of response. 2) Better selection of therapy. Molecular imaging before therapy can be used to predict the aggressiveness of disease and help select the best therapy. Imaging during or after therapy will be a sensitive measure of tumor response. When therapy changes a critical tumor function, it can be continued with confidence; when therapy fails to impair a critical tumor function, it is unlikely to be effective but may still damage normal tissues. Each project tests our hypothesis that molecular imaging can assess and predict cancer response to treatment. Imaging will be used to characterize tumors of the brain, head & neck, breast and thyroid as well as lymphoma, sarcoma and pheochromocytoma. Molecular imaging provides a versatile tool with excellent spatial and molecular resolution. FDG is valuable, but other radiopharmaceuticals can characterize tumors with much more specificity. Our studies use PET to evaluate aspects of tumor growth and factors that limit the response of a tumor to therapy. PET provides information from the whole body and will be used to assess regional heterogeneity. Short-lived isotopes permit studies with different tracers in a single imaging session, enabling quantitative assessment of multiple tumor properties. When appropriate, molecular pathology complements molecular imaging, with images used to direct the site of biopsy. New assays are used to test statistical correlations between imaging and in vitro analysis of tissue samples so that each use of a radiopharmaceutical is based on careful validation in humans. The projects use similar PET data analysis and statistical tests that are convenient but realistic. This research program is strongly interdisciplinary, drawing together experts in imaging with experts in clinical and laboratory oncology. The group that started this research remains largely intact and several new investigators have been added. Our goals are ambitious and the methods complex, but our collective effort will make a significant and valuable contribution to oncology.